The impact of complex karyotype identified by conventional cytogenetics on survival outcomes of 1,000 patients with newly diagnosed myeloma (NDMM).
Authors: Dabedochukwu Obiekwe, Nisha Joseph, Craig C. Hofmeister, Dhwani Almaula, Leonard T. Heffner, Vikas Anand Gupta, Lawrence Boise, Madhav V. Dhodapkar, Sagar Lonial, Ajay K. Nooka, Jonathan L. Kaufman
Journal: Journal of Clinical Oncology (2022)

8063 Background: Complex karyotype (CK), defined as two or more cytogenetic abnormalities on conventional metaphase cytogenetics, is not routinely used for the risk-stratification or treatment determination in patients with newly diagnosed myeloma (NDMM). Here, we present a retrospective analysis utilizing our institutional data of NDMM patients treated with RVD and a risk-adapted maintenance strategy at the Winship Cancer Institute of Emory University to assess the impact of CK on long-term outcomes. Methods:1000 consecutive NDMM patients treated with RVD induction therapy (R25mg/day, days 1-14; V1.3 mg/m 2 , days 1,4,8,11 and D40mg once/twice weekly as tolerated) were identified from January 2007 to August 2016. Demographics, clinical characteristics and outcome data for patients were obtained from our institutional review board-approved myeloma database. Responses were evaluated per IMWG Uniform Response Criteria. Results: The median age of this cohort was 61 (range 16-83). Notable patient characteristics include: M/F 54.6%/45.4%, W/AA 61.8%/35.9%; ISS I/II/III 45.8%/30.8%/23.4%. R-ISS I/II/III 39.9%/48.7%/11.5%; Isotype IgG/IgA/FLC 59.2%/19.0%/15.7%; standard risk(SR)/high risk(HR) 71.2%/15.8%. ISS data was available for 75% of patients; R-ISS was available for 41% of patients. HR disease defined as the presence of t(4;14), t(14;16), del(17p) and/or CK. Frequency of specific CTG abnormalities were:14.9% with +1q21, 8.3% with del(1p),12.1% with t(11;14), 25.7% with del(13), 13.9% with CK, 2.8% with t(14;16), 10% with del(17p), and 4.8% with t(4;14). 11.9% of patients were classified high risk by FISH alone, 10.0% of patients were classified as high risk by complex karyotype(CK), and 3.9% of patients were classified as high risk by the presence of both high-risk FISH and CK. With a median follow up of 88.4 months, the median PFS (mPFS) for patients HR by FISH alone was 47.6 months (95% CI 35.2-59.9), for HR by CK alone was 46.9 months (95% CI 28.1-65.7) and for HR by both was 24.0 months (95% CI 8.3-39.7). The mOS for HR by FISH alone was 94.7 months (95% CI 74.4-115.1),HR by CK alone was 105.9 months (95% CI 60.8-151.0) and HR by both was 41.0 months (95% CI 24.2-57.8). Conclusions: CK by conventional metaphase cytogenetics is not currently included in the risk-stratification or risk stratification models of NDMM patients. In patients with a complex karyotype at time of diagnosis, mPFS and mOS is essentially the same as patients classified HR by FISH abnormalities. When compared to SR patients, prognosis is significantly worse, therefore the standard treatment approach is likely insufficient. As many centers do not routinely perform chromosome analysis, this highlights a gap in providing appropriate risk-stratified care. Moreover, NDMM with HR features by FISH and CK portends a poor prognosis for which alternative treatment strategies may need to be explored.